Origin and Differences from Natural Alkaloids
The raw material for producing drugs in this group is the ergot sclerotium from the parasitic fungus Claviceps purpurea, which infects rye crops. Structurally, all members of this group are derivatives of 6-methylergoline (D-lysergic acid). Key agents include dihydroergotamine, dihydroergotoxine, and dihydroergocryptine.
Chemical modification (dihydrogenation) significantly alters the pharmacological profile of these molecules, eliminating several adverse effects characteristic of natural compounds.
| Pharmacological Effect | Natural Alkaloids | Dihydrogenated Derivatives |
|---|---|---|
| Effect on the Uterus | Increases myometrial tone | No stimulatory effect |
| Direct Vascular Effect | Pronounced vasoconstriction | Reduced vasoconstrictive action |
| $\alpha$-Adrenoceptor Blockade | Moderate | Significantly stronger |
Dihydroergotamine: Profile of a Prototype Drug
Dihydroergotamine is considered the benchmark representative of this group. Its mechanism of action comprises two main components: non-selective blockade of $\alpha_1$- and $\alpha_2$-adrenoceptors and partial agonism at serotonin receptors. This results in diverse effects across different vascular beds.
- Peripheral Effects: The drug causes pronounced peripheral vasodilation, leading to a decrease in systemic blood pressure (BP).
- Central Effects: By stimulating serotonin receptors, dihydroergotamine exerts a tonic effect on cerebral blood vessels.
In clinical practice, dihydroergotamine (brand name Dihydroergot, typically formulated as mesylate/methanesulfonate) is widely used for aborting acute migraine attacks. Specific indications also include vasospastic angina and orthostatic hypotension (in the latter case, the effect is achieved via venotonic action). The drug can be administered intranasally as a spray, parenterally, or orally in drop form.
Combination Drugs and Analogues
In addition to pure alkaloids, medical practice utilizes combinations and synthetic analogues with an expanded spectrum of activity.
Vasobral (Vasobral) A combination drug containing the dihydrogenated alkaloid dihydroergocryptine and the trimethylxanthine derivative caffeine. Its pharmacodynamics involve $\alpha$-adrenoceptor blockade and subsequent vasodilation. Vasobral is prescribed for cerebrovascular disease, post-stroke rehabilitation, peripheral circulation disorders, and cochleovestibular disorders (hearing and balance disturbances).
Nicergoline (Nicergoline) Nicergoline is an ergot alkaloid derivative in which the ergoline nucleus is linked to a bromo-substituted nicotinic acid residue, providing a dual mechanism of action:
- $\alpha$-adrenoceptor blocking activity.
- Myotropic spasmolytic activity.
Nicergoline induces pronounced dilation of cerebral and peripheral vessels while exerting minimal effect on systemic blood pressure. Additionally, it inhibits platelet aggregation and possesses a nootropic effect (enhancing memory and attention). It is used for chronic cerebrovascular disorders, migraine, and peripheral vascular disease. Notably, it should be taken before meals, and its therapeutic effect develops slowly, requiring a prolonged course of treatment lasting several months.
Proroxan (Pyrroxan)
Proroxan stands out due to its ability to block both peripheral and central $\alpha_1$- and $\alpha_2$-adrenoceptors, with a particularly important clinical action on hypothalamic receptors.
Blockade of peripheral adrenoceptors, predominantly in arterioles and precapillaries, leads to vasodilation and reduced blood pressure. Beyond its antihypertensive action, proroxan exhibits sedative, anti-withdrawal, and antipruritic effects.
It is valuable in managing hypertensive and sympathoadrenal crises (especially in hypothalamic syndrome with hypertension). It is also successfully utilized in addiction medicine to alleviate opioid or alcohol withdrawal symptoms, in dermatology for pruritic allergic dermatoses, and for vestibular disorders, including Meniere's disease and motion sickness.